High Dose Vitamin C Intravenous Infusion in Patients With Resectable or Metastatic Solid Tumor Malignancies

NCT03146962 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 1610017688
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 2

Brief Summary

This is a multicenter, single arm, 3-cohort, open-label trial of high dose Vitamin C intravenous infusion in subjects with solid tumor malignancies who are eligible for resection (cohort A) or with extended RAS (e.g.KRAS or NRAS) or BRAF mutation metastatic cancer who have received prior systemic treatment (cohort B). Cohort C will involve patients with colorectal cancer having an extended RAS or BRAF mutation who are amenable for localregional therapy of hepatic metastases with Yttrium-90 radioembolization.

Conditions

Colorectal Cancer; Pancreatic Cancer; Lung Cancer

Outcome Measures

Primary Outcomes (3)

• Pathologic Response Based on Tumor Regression Grading in Cohort A Patients

  Number of patients with partial or complete pathological response in surgically resected tumor tissue: Pathological response rate is the number of patients with partial or complete pathological response in surgically resected tumor tissue. Pathologic response was assessed by tumor regression grade. This is a pathologic assessment of the amount of residual cancer cells in the specimen and the degree of fibrosis in the sample specimen. A completer response is 0% residual cancer cells. A partial response is 10-50% residual cancer cells, and no response is \>50% residual cancer cells within the tumor specimen.

  cohort A - 8 weeks

• 3-month Disease Control Rate (DCR) Will be Evaluated Using RECIST v 1.1 in Cohort B Patients.

  Percentage of patients with complete response, partial response, or stable disease as a result of their therapy at 3 months

  Cohort B - 3 months

• Maximal Tolerated Dose of High Dose Vitamin C in Combination With Y90 Radioembolization

  Maximal tolerated dose will be evaluated by assessment of dose limiting toxicities for multiple dose levels. Dose limiting toxicity will be defined as any grade 3-4 adverse event possibly, probably, or definitely attributed to vitamin C therapy in the 21 days of protocol therapy. In any group of 3 patients, if one patient experiences dose limiting toxicity, the group will be expanded by 3 additional patients (eg. 6 for that group). If, at any dose level, 2 or more patients experience a dose limiting toxicity, the maximal tolerated dose will be reached, and further dose escalation will not be pursued. The dose level may then be expanded up to 10 additional patients to confirm the safety and toxicity at that dose level.

  Cohort C - 16 weeks

Secondary Outcomes (5)

• Progression-free Survival (PFS)

  cohort B - up to 6 months

• Objective Response Rate (ORR)

  cohort B - up to 6 months cohort C - 16 weeks

• Time to Maximum Concentration and Half-life of Vitamin C (t1/2) in Hours in Cohort B

  Up to 24 hours post-infusion

• Safety of High Dose Vitamin C Administration Using CTCAE 4.03.

  Adverse events were assessed from the start of study treatment to 30 days after the last infusion of vitamin C. For Cohort A and C, this was approximately 2 months. For Cohort B this was about a 6 month duration.

• Maximum Concentration of Vitamin C in Hours in Cohort B

  Up to 24 hours post-infusion

Other Outcomes (3)

• In Vitro Activity of Vitamin C in Tumor Organoids

  cohort A - 8 weeks, cohort B - up to 6 months

• Exploratory Biomarker Samples From Tumor Tissue Will be Collected at the Time Points Specified in the Protocol

  cohort A - 8 weeks, cohort B - up to 6 months, Cohort C - 16 weeks

• Pharmacodynamic Samples From Tumor Tissue Will be Collected at the Time Points Specified in the Protocol.

  cohort A - 8 weeks, cohort B - up to 6 months, Cohort C - 16 weeks

Study Arms (10)

Cohort A: Vitamin C + Surgery

EXPERIMENTAL

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks.

Drug: Vitamin C

Cohort B: Vitamin C Only

EXPERIMENTAL

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for up to 6 months.

Drug: Vitamin C

Cohort C: Vitamin C + Y-90 Dose Level 1

EXPERIMENTAL

Vitamin C will be administered at a dose of 0.5 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C.

Drug: Vitamin C

Cohort C: Vitamin C + Y-90 Dose Level 2

EXPERIMENTAL

Vitamin C will be administered at a dose of 0.75 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C.

Drug: Vitamin C

Cohort C: Vitamin C + Y-90 Dose Level 3

EXPERIMENTAL

Vitamin C will be administered at a dose of 0.75 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. A single dose of Vitamin C at 0.5g/kg will also be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment.

Drug: Vitamin C

Cohort C: Vitamin C + Y-90 Dose Level 4

EXPERIMENTAL

Vitamin C will be administered at a dose of 1 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. A single dose of Vitamin C at 0.5g/kg will also be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment.

Drug: Vitamin C

Cohort C: Vitamin C + Y-90 Dose Level 5

EXPERIMENTAL

A single dose of Vitamin C at 0.75g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy.

Drug: Vitamin C

Cohort C: Vitamin C + Y-90 Dose Level 6

EXPERIMENTAL

A single dose of Vitamin C at 0.75g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy.

Drug: Vitamin C

Cohort C: Vitamin C + Y-90 Dose Level 7

EXPERIMENTAL

A single dose of Vitamin C at 1g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy.

Drug: Vitamin C

Cohort C: Vitamin C + Y-90 Dose Level 8

EXPERIMENTAL

A single dose of Vitamin C at 1.25g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy.

Drug: Vitamin C

Interventions

Vitamin C DRUG

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

Also known as: Ascorbic Acid

Cohort A: Vitamin C + Surgery; Cohort B: Vitamin C Only; Cohort C: Vitamin C + Y-90 Dose Level 1; Cohort C: Vitamin C + Y-90 Dose Level 2; Cohort C: Vitamin C + Y-90 Dose Level 3; Cohort C: Vitamin C + Y-90 Dose Level 4; Cohort C: Vitamin C + Y-90 Dose Level 5; Cohort C: Vitamin C + Y-90 Dose Level 6; Cohort C: Vitamin C + Y-90 Dose Level 7; Cohort C: Vitamin C + Y-90 Dose Level 8

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥ 18 years of age.
• Patients with histologically proven early stage or locally advanced colorectal adenocarcinoma, lung cancer or pancreatic cancer, who are eligible for resection (cohort A).
• Patients with inoperable, metastatic extended RAS (e.g. KRAS or NRAS) or BRAF mutant colorectal adenocarcinoma, lung cancer and pancreatic cancer, or other solid tumor, who have received at least 1 line of treatment for metastatic disease (cohort B).
• Patients with metastatic cancer with an extended RAS (e.g. KRAS or NRAS) or BRAF mutation with liver metastases amenable to Y90 radioembolization (cohort C).
• ECOG performance status 0-1.
• Life expectancy of at least 6 months.
• All women of child-bearing potential and all sexually active male patients must agree to use effective contraception.

You may not qualify if:

• Patients with uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure (NYHA class III and IV), uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements (Appendix B: New York Heart Association (NYHA) Classifications).
• Patients with active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, unstable angina pectoris, or uncontrolled congestive heart failure (NYHA class III and IV) (Appendix B: New York Heart Association (NYHA) Classifications).
• Patients who have received an investigational drug within 21 days of the first dose of study drug.
• Patients who are pregnant or lactating.
• Patients who are known to be positive for the human immunodeficiency virus (HIV). The effect of Vitamin C on HIV medications is unknown. Note: HIV testing is not required for eligibility, but if performed previously and was positive, the patient is ineligible for the study.
• Patient who are receiving drugs which are known to interact with Vitamin C, potential risk and eligibility will be evaluated individually by the investigator. a. Most of the known interactions with vitamin C are from oral use and acidification of the stomach lining. There are few known interactions with high dose intravenous vitamin C. We recommend not using deferoxamine as there may be an association with ventricular dysfunction (unknown mechanism).
• Patients who have uncontrolled or severe hyponatremia, hypernatremia, SIADH, hypokalemia, hyperkalemia, hypomagnesemia, or hypermagnesemia
• Patients who have uncontrolled or severe coagulopathies or a history of clinically significant bleeding within the past 6 months, such as hemoptysis, epistaxis, hematochezia, hematuria, or gastrointestinal bleeding.
• Patients who require therapeutic doses of warfarin
• Patients who have uncontrolled seizure disorder, ascites, iron overload, edema, or dehydration.
• Patients who have glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis, or other conditions predisposing patient to hemolysis.
• Patients who have a known history of recurrent oxalate renal calculi or multiple oxalate.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Stand Up To Cancer: collaborator

Study Sites (2)

New York-Presbyterian Brooklyn Methodist Hospital

Brooklyn, New York, 11215, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Pancreatic Neoplasms; Lung Neoplasms

Interventions

Ascorbic Acid

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Results Point of Contact

• Title: Dr. Manish Shah, Sponsor-Investigator
• Organization: Weill Cornell Medicine

mas9313@med.cornell.edu

646-962-6200

Study Officials

• Manish Shah, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2017
• First Posted: May 10, 2017
• Study Start: March 29, 2017
• Primary Completion: April 21, 2023
• Study Completion: April 21, 2023
• Last Updated: May 2, 2024
• Results First Posted: May 2, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)